Dr Pant on the Investigation of Zanidatamab in Biliary Tract Cancer

Shubham Pant, MD, MBBS, associate professor, departments of Investigational Cancer Therapeutics and Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the rationale for the phase 2b HERIZON-BTC-01 trial (NCT04466891) and shares the results with zanidatamab in previously treated HER2-amplified biliary tract cancer.

Investigators presented data from the multicenter, open-label, single-arm trial at the 2023 ASCO Annual Meeting. The HERIZON-BTC-01 study evaluated the anti-tumor activity of the HER2-targeted bispecific antibody zanidatamab in patients with HER2-amplified, locally advanced or metastatic biliary tract cancer.

Biliary tract cancer is an uncommon malignancy that is difficult to treat and there are 3 main subtypes: gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma, Pant begins. Notably, HER2-positive expression differs among these 3 subtypes. For example, HER2 positivity is seen in between 20% and 30% of gallbladder cancer, between 10% and 20% of extrahepatic cholangiocarcinoma, and in 5% of intrahepatic cholangiocarcinoma, Pant explains. This unmet clinical need prompted investigators to launch a phase 1 trial to target patients with HER2-amplified biliary tract cancer. Results from the trial served as the basis for the phase 2b global study to evaluate the efficacy of zanidatamab in this patient population, Pant says.

Results from the trial demonstrated that the confirmed objective response rate (ORR) in cohort 1 (n = 80) was41.3% (95% CI, 30.4%-52.8%) and the median duration of response was 12.9 months (range, 1.5-16.9+), which was found to be robust and durable, Pant continues. Notably, HER2 was tested by immunohistochemistry and in situ hybridization, Pant says, adding that all patients were amplified by 2+ or 3+ in cohort 1.